The long-term objective of this Mentored Clinical Scientist Research Career Development (K08) Award is to develop the candidate's skills in combining multi-modal neuroimaging with behavior analytic research so that he may become one of the first independent scientists to integrate applied behavioral analysis with clinical neuroscience investigation in the study of children with serious neurodevelopmental disorders. The candidate's specific research goal is to apply neuroimaging techniques to evaluate specific targeted behavior analytic interventions for children with fragile X syndrome. To accomplish this goal, the candidate will be mentored by experts in the fields of behavioral neurogenetics and neuroimaging and will pursue an educational program that includes advanced seminars in neuroimaging as well as formal coursework in the areas of cognitive psychology', genetics and neuroscience. The primary goal of the proposed research project is to target specific cognitive and behavioral weaknesses shown by individuals with fragile X syndrome (math and money skills) for intensive behavioral intervention. The efficacy of this intervention will be evaluated using specific neuroimaging metrics as well as behavioral measures. By understanding the neural correlates of behavior change, these neuroimaging metrics will be employed in statistical models to improve prediction of response outcome. Two subject groups will be exposed to the interventions: a group of children with fragile X syndrome (FXS), and a group of age- gender and IQ-matched subjects with a non-specific form of developmental disability (NSDD). Both groups will receive the neuroimaging prior to and following the intensive intervention conducted at Stanford over three days. It is hypothesized that effective intervention (as demonstrated by significant behavioral or cognitive change) will be associated with profiles of brain activation reflecting "normalization" of functional connectivity and/or compensatory activation. The candidate will also investigate whether particular profiles of activation at baseline predict response. Only limited information is available concerning optimal methods for enhancing cognitive abilities in individuals with FXS. If this intervention is found to be an effective method for learning in individuals with FXS, the technique could be rapidly translated into the clinical and educational environments, thus benefiting many children and adolescents with this disorder. [unreadable] [unreadable] [unreadable]